Immunogenicity of BCG in HIV-exposed and non-exposed infants following routine birth or delayed vaccination

Abstract

SUMMARY BACKGROUND Human immunodeficiency virus (HIV) exposed infants are at high risk of Mycobacterium tuberculosis exposure, have high rates of progression to tuberculosis (TB) disease and are at significant risk of bacille Calmette-Guérin (BCG) induced adverse events. OBJECTIVE To evaluate a delayed BCG vaccination strategy in HIV-exposed infants. DESIGN A randomised trial of routine BCG vaccination given at birth compared to 14 weeks of age in HIV-exposed non-infected and non-HIV-exposed infants to investigate longitudinal BCG-induced immune responses using a 7-day whole blood interferon-gamma (IFN-γ) enzyme-linked immunosorbent assay. RESULTS A significantly higher proportion of infants had positive responses to M. tuberculosis purified protein derivative (PPD) and BCG at 14 weeks in the birth vs. delayed vaccination groups (P = 0.001 for both). This difference was no longer apparent at weeks 24 or 52. Among infants vaccinated at birth, the 14-week IFN-γ response to M. tuberculosis PPD was lower among HIV-exposed than non-exposed infants (276.5 pg/ml vs. 790.2, P = 0.048). Among all infants, there were significant correlations between the magnitude of IFN-γ responses to BCG, M. tuberculosis PPD, TB 10.4 and culture filtrate protein 10/early secreted antigenic target 6. CONCLUSIONS The timing of vaccination had limited effect on BCG-induced IFN-γ responses, which waned considerably over 1 year despite initial vigorous responses in both vaccination groups. The lower responses in HIV-exposed non-infected infants suggest potentially altered mycobacterial immunity early in life.

Delayed BCG immunization does not alter antibody responses to EPI vaccines in HIV-exposed and -unexposed South African infants

“…These data are consistent with our own and other published data. [5,23] The higher observed antibody responses to Hib and pertussis amongst HEU infants may be due to reduced maternal-infant placental antibody transfer in the presence of maternal HIV infection. Jones et al showed that HEU infants had lower concentrations of specific antibodies at birth than HUU infants to Hib, wP, pneumococcus and tetanus vaccines, in the identical study setting.…”

“…BCG coverage was estimated at 99% during 2005. [22] Eligibility and randomization Recruitment, enrolment, BCG vaccination and surveillance were carried out as previously described [23]. Briefly, this was an individual, single-blinded, exploratory randomized Phase 2 clinical trial investigating immunological effects of early versus delayed BCG vaccination in HIV-exposed and -unexposed infants (DOH-27-1106-1520).…”

“…Infant HIV testing and clinical follow-up were performed as previously described. [23] Briefly surface antigen (HBsAg) were quantified using a semi-automated ELISA method (AxSym HBsAb, Abbott Diagnostics, measuring range: 2-1000 mIU/ml). Hib antibody level was classified as protective if >1 mg/ml and non-protective level if ≤1 mg/ml.…”

HIV induced suppression of host immunity: relevance to <i>Mycobacterium tuberculosis</i> infections

“…Leading candidate vaccines for either of pathogen have not been effective. However, these studies are not conclusive and reported contrasting findings [200][201][202][203][204]. It has become a necessity to recalibrate many fine intricacies of the immune system that were not prioritized earlier.…”

Tuberculosis and HIV—An Update on the “Cursed Duet” in Children

“…However, HIV+ infants not identified in infancy are at high risk for disseminated BCG. In South Africa, BCG induced immune responses at 52 weeks of age did not differ in HEU infants receiving the vaccine at birth compared to 14 weeks of age (36). A similar study is currently underway in Uganda (NCT02606526).…”